CASE REPORT Open Access

The renal manifestations of type 4 familialpartial lipodystrophy: a case report andreview of literatureRu-Xuan Chen1, Lei Zhang2, Wei Ye2, Yu-Bing Wen2, Nuo Si3, Hang Li2, Ming-Xi Li2, Xue-Mei Li2 and Ke Zheng2,4*

Abstract

Background: Lipodystrophy syndromes are rare disorders of variable body fat loss associated with potentiallyserious metabolic complications. Familial partial lipodystrophy (FPLD) is mostly inherited as an autosomal dominantdisorder. Renal involvement has only been reported in a limited number of cases of FPLD. Herein, we present a rarecase of proteinuria associated with type 4 FPLD, which is characterized by a heterozygous mutation in PLIN1 andhas not been reported with renal involvement until now.

Case presentation: A 15-year-old girl presented with insulin resistance, hypertriglyceridaemia, hepatic steatosis andproteinuria. Her glucose and glycated haemoglobin levels were within normal laboratory reference ranges. A novelheterozygous frameshift mutation in PLIN1 was identified in the patient and her mother. The kidney biopsy showedglomerular enlargement and focal segmental glomerulosclerosis under light microscopy; the electron microscopyresults fit with segmental thickening of the glomerular basement membrane. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) decreased 24-h protein excretion.

Conclusions: We report the first case of proteinuria and renal biopsy in a patient with FPLD4. Gene analysisdemonstrated a novel heterozygous frameshift mutation in PLIN1 in this patient and her mother. Treatment withACEI proved to be beneficial.

Keywords: Familial partial lipodystrophy, PLIN1, Proteinuria, Focal segmental glomerulosclerosis

BackgroundLipodystrophy syndromes are a group of rare disorderscharacterized by variable loss of body fat. Adipose tissueloss may affect nearly the entire body (generalized) oronly certain regions (partial) or small areas (localized,usually caused by insulin injections). Patients are predis-posed to potentially serious metabolic complications as-sociated with insulin resistance, including diabetesmellitus, hypertriglyceridaemia, and steatohepatitis.Other common clinical manifestations include acantho-sis nigricans, polycystic ovarian syndrome, hypertension,cardiomyopathy, and arrhythmias. Patients can also haverenal dysfunction, which may present as proteinuria,

diabetic nephropathy, focal segmental glomerulosclerosis(FSGS) or mesangiocapillary glomerulonephritis(MCGN) [1, 2].Familial partial lipodystrophy (FPLD) is characterized

by loss of subcutaneous fat from the extremities and thetrunk. Fat distribution is typically normal in early child-hood, followed by onset of partial lipodystrophy aroundpuberty. FPLD is mostly inherited as an autosomal dom-inant disorder. There are several subtypes of FPLD. Type2 FPLD (Dunnigan-type, with missense mutations inLMNA; OMIM #151660) is the most common, and type3 FPLD (with heterozygous mutations in PPARG; OMIM#604367) is the second most common subtype. Type 2and type 3 FPLD account for more than 50% of all casesof FPLD [1, 3]. Type 4 FPLD (with heterozygous muta-tions in PLIN1; OMIM #613877) is a rare subtype ofFPLD, which is newly recognized and only reported infive unrelated families [4, 5]. This subtype is also desig-nated type 5 FPLD by some scholars [6]. Lipodystrophy

* Correspondence: kellyz_0_67@163.com2Department of Nephrology, Peking Union Medical College Hospital, ChineseAcademy of Medical Sciences, Beijing, China4Present address: Peking Union Medical College Hospital (East), No. 1Shuaifuyuan, Dongcheng District, Beijing 100730, ChinaFull list of author information is available at the end of the article

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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is most prominent in the lower limbs and buttocks.The PLIN1 gene codes for perilipin 1, which is a lipiddroplet coat protein predominantly expressed in adi-pocytes [7]. It is required for optimal lipid incorpor-ation. Here, we present a unique case of renalinvolvement in an adolescent patient with type 4FPLD. An unreported heterozygous frameshift muta-tion in PLIN1 was identified in the patient and hermother. Until now, no renal involvement has been re-ported in type 4 FPLD. This is the first case of pro-teinuria and renal biopsy in a patient with type 4FPLD.

Case presentationA 15-year-old Chinese female was referred to theDepartment of Nephrology, Peking Union MedicalCollege Hospital because of proteinuria. She wasnoted to have proteinuria (protein excretion 2–3 g/24 h, maximum 3.1 g/24 h) at the age of 14 years.She had a history of hypertriglyceridaemia (triglycer-ide, 3.4 mmol/L) and nonalcoholic steatohepatitis(proven by liver biopsy, Grade 1–2, Stage 2 [8]) atthe age of 12 years, and insulin-resistant diabetes atthe age of 13 years (fasting insulin, 172.4 μU/mL;fasting c-peptide, 9.66 ng/mL; fasting glucose, 5.8 mmol/L; 2-h postprandial glucose, 15.5 mmol/L).Pelvic ultrasound revealed polycystic ovaries, and herserum testosterone concentration was 68 ng/dL. Me-narche occurred at the age of 13 years and wasregular thereafter. She was told to follow a low-carbohydrate, low-fat diet and was given metformin.With these treatments, her fasting and postprandial

glucose level stayed normal, and glycated haemoglo-bin level was 5.5–5.8%. She had no history of hyper-tension, and she was a recreational jogger. Hermother, aunt and grandfather had middle-age-onsetinsulin-resistant diabetes.On admission, her body mass index (BMI, the weight in

kilograms divided by the square of the height in metres)was 22.9. Clinical examination revealed prominent muscu-lar appearance of the calves (Fig. 1c). Lipoatrophy was notobvious. Acanthosis nigricans was present in the inguinal,nuchal and axillary regions (Fig. 1a). She had slightly ex-cessive body hair on upper and lower limbs (Fig. 1b).Laboratory evaluation revealed normal serum albumin

(47 g/L), decreased creatinine (36 μmol/L), and elevated es-timated glomerular filtration rate (154 mL/min/1.73 m2,Revised Schwartz Formula). Urine protein excretion was 1.72 g/24 h. Complement components C3 and C4 were 1.630 g/L (range 0.73–1.46 g/L) and 0.166 g/L (range 0.1–0.4 g/L), respectively. Complement factor H was normal, andC3 nephritic factor was not detected. Auto-antibodies andserum immunoglobulins were normal. Renal ultrasoundshowed both kidneys to be of normal size (length of rightkidney was 11.5 cm, length of left kidney was 10.7 cm) andappearance. There was no evidence of diabetic retinopathyor other diabetes-related microvascular complications. Herbody fat percentage was 24.7% (TBF-410 Total Body Com-position Analyzer, Tanita, Japan). Whole body magnetic res-onance diffusion-weighted imaging revealed mildly reducedsubcutaneous fat mass, hepatic steatosis, and polycysticovaries (Fig. 2).Considering the early onset of metabolic abnormal-

ities, whole exome sequencing was performed to detect

Fig. 1 Clinical appearance of the patient. a Acanthosis nigricans in the axillary region. b Slightly excessive body hair on lower limbs. c Muscularappearance of the calf

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mutations in the blood samples of the patient and herparents. She and her mother were noted to have a het-erozygous insertion of thymine in exon 8 (c.1201_1202insT) of the PLIN1 gene (Fig. 3), which predicted aframeshift translation leading to the synthesis of 165 ab-errant amino acids (p.Y401Lfs*165) and a mutated pro-tein with an aberrant C-terminal. We detected nomutations in genes previously implicated in lipodystro-phies (LMNA, PPARG, CIDEC, LIPE, ADRA2A, AKT2,PCYT1A, AGPAT2, BSCL2, CAV1, and PTRF).The BMI of the patient’s mother was 22.1. She did not

have acanthosis nigricans. She was noted to have gesta-tional diabetes at the age of 32 years, and she still had

Fig. 2 Magnetic resonance images of the patient. Whole body magnetic resonance diffusion-weighted imaging (a) demonstrated mildly reducedsubcutaneous fat mass. Axial T2-weighted images at the level of breast (b1), abdomen (b2), pelvic region (b3) and thigh (b4) illustrated fat distributionof the body and extremities. Image b3 revealed polycystic ovaries. Dual phase T1-weighted images (c1 and c2) showed mild signal loss on out-of-phaseimages (c2), which is consistent with hepatosteatosis

Fig. 3 Result of DNA Sanger sequencing analysis of the PLIN1 gene.Within exon 8, the insertion of thymine in PLIN1 allele 2 wasidentified in the patient and her mother but in not her father

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diabetes mellitus after the birth of her daughter.While she was on insulin treatment, her fasting glu-cose was 5.6–7.2 mmol/L. She also had dyslipidaemia(LDL-cholesterol, 4.13 mmol/L; total cholesterol, 5.69 mmol/L; triglyceride, 0.78 mmol/L) treated withdiet control and a statin. She had regular healthcheck-ups in recent years. Her urine tests and renalfunction tests were normal. Ultrasound showed nosign of hepatic steatosis. Her father carried no muta-tion, and he was generally healthy. He did not havediabetes, dyslipidaemia, fatty liver, or proteinuria. Thepatient’s maternal grandfather had diabetes. One uncleand one cousin on the maternal side had hepaticsteatosis (according to ultrasound results). In addition,one maternal aunt had diabetes, dyslipidaemia andhepatic steatosis (Fig. 4).Renal biopsy was performed on the patient. Immuno-

fluorescence (IF) microscopy showed no immunoglobu-lin deposits. Light microscopy (LM) revealed that in theabsence of significant background tubulointerstitial dam-age, 1 out of 17 glomeruli obtained was globally scler-osed, 2 glomeruli displayed segmental sclerosis (onesegmental sclerosis adhered to Bowman’s capsule and in-volved the perihilar region, the other one was concomi-tant with exudative lesion (Fig. 5c)), and the remainingglomeruli displayed mild mesangial hypercellularitywithout matrix expansion (Fig. 5b). Glomerular enlarge-ment was observed (Fig. 5a), with average glomerulardiameter being 230 μm and maximum diameter being251 μm. Transmission electron microscopy (EM) re-vealed focal thickening of the glomerular basementmembrane (GBM) and mild focal effacement of footprocesses; mild expansion in mesangial matrix was alsoshown under EM (Fig. 5d); no electron-dense depositswere present.She was given benazepril (10 mg per day, gradually ti-

trated to 20 mg twice a day) and metformin. Benazeprilwas well-tolerated, with no cough, hypotension or hyper-kalaemia. After 1 month, her renal protein excretion was

decreased to 0.81 g/24 h. Serum creatinine level was40 μmol/L.

DiscussionThe estimated prevalence of FPLD is 1 in 1,000,000people in the general population. FPLD is more commonin Caucasians (79%) and has a female predominance(83%) [6].Type 4 FPLD is a rare autosomal dominant disorder

caused by mutations in the PLIN1 gene leading to de-fective adipogenesis and dysregulated lipolysis. To date,only five families with type 4 FPLD have been reported,and no case of type 4 FPLD has been reported in Asia.The PLIN1 gene codes for perilipin 1, which is the

most abundant phosphoprotein in adipocytes. Perilipin 1associates with the phospholipid surface layer of the lipiddroplet and is critical for optimal lipid metabolism [7]. Itregulates lipid accumulation and release from the lipiddroplets primarily through the regulation of lipases, in-cluding adipose tissue triglyceride lipase (ATGL) andhormone-sensitive lipase (HSL). ATGL and HSL catalysethe hydrolysis of tri- and diacylglycerol, releasing fattyacids and monoacylglycerol [9]. Perilipin-null mice werelean and resistant to obesity and exhibited increasedbasal lipolysis but diminished catecholamine-stimulatedlipolysis [10]. Loss-of-function mutations in the PLIN1gene were reported in patients with type 4 FPLD [4, 5].Type 4 FPLD is an autosomal dominant disorder. All re-ported mutations were heterozygous frameshift muta-tions affecting the COOH-terminus of perilipin 1,leading to the failure of the proteins to prevent ABHD5(αβ-hydrolase domain containing 5) from activatingATGL [4, 11]. One mutant (439 fs mutant) had a lowerexpression level and shorter half-life than the wild-typeprotein [4], and the other two (404 fs and 398 fs mu-tants) failed to bind ABHD5 [11]. Patients with PLIN1mutations reportedly had higher basal lipolytic rates andsmaller adipocytes with increased infiltration of macro-phages and fibrosis in the adipose tissue [4, 5]. Increasedplasma fatty acids can lead to lipid accumulation in ec-topic sites, such as the liver and skeletal muscle, wherethey are instrumental in causing insulin resistance [12].In this case, we identified a novel heterozygous frame-

shift mutation (c.1201_1202insT) affecting the carboxy-terminus (401 fs) of perilipin 1. The mutation site wasbetween two previously reported mutations (c.1191_1192delAG, and c.1308-1309delTG) [4, 5]. Amino acids380–427 in the human sequence of perilipin 1 wereshown to be crucial for ABHD5 binding [13]. We thusinferred that this p.Y401Lfs*165 mutant could not effect-ively bind ABHD5 and was likely to be pathogenic. Thefact that the patient’s mother (a carrier of this mutation)was affected, while the patient’s father (without this mu-tation) was generally healthy, was supportive of the

Fig. 4 Pedigree of the patient’s family. The patient is designated bythe arrow

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pathogenicity of this mutation. Furthermore, this het-erozygous frameshift variant had not been reported indatabases of the general population including GNO-MAD (genome aggregation database), ExAC (exomeaggregation consortium), 1000 Genomes, and dbSNP(single nucleotide polymorphism database).As adipose tissues have pivotal roles in maintaining

healthy metabolic homeostasis, FPLD patients usuallyhave metabolic complications including insulin resist-ance, diabetes, dyslipidaemia and hepatic steatosis [1].The severity of the metabolic complications may beroughly proportional to the extent of lipoatrophy.However, in this case, the patient had prominent in-sulin resistance, dyslipidaemia and hepatic steatosis,but only mildly reduced subcutaneous fat. The pa-tient’s mother, who carried the same heterozygousframeshift mutation, had milder symptoms. She onlyhad diabetes and mild dyslipidaemia. Unfortunately,we did not have the opportunity to assess themother’s fat mass and fat distribution. However, herbody type appeared normal. Possible explanations forthe variability of the phenotype of this mutation inthis family include interindividual variability in thegene expression.

Renal dysfunction of lipodystrophies (familial and ac-quired) can present as proteinuria, diabetic nephropathy,FSGS or MCGN [1, 2]. Different renal pathologies havebeen recognized in cases of generalized lipodystrophy(familial or acquired) [14], and renal biopsy revealedFSGS in four patients, MCGN in two patients, and dia-betic nephropathy in one patient. The majority treatedwith recombinant leptin demonstrated a reduction inproteinuria and hyperfiltration. Approximately 22% ofpatients with acquired partial lipodystrophy developedMCGN type II (dense deposit disease) after a median ofapproximately 8 years following the onset of lipodystro-phy [15]. These patients usually had low plasma C3and elevated C3 nephritic factor; the latter wasthought to cause lysis of adipose tissue [16]. Thefirst case of biopsy-proven MCGN type II associatedwith FPLD was reported in a case of type 2 FPLD(with mutation in the LMNA gene), with no hypo-complementaemia or evidence of C3 nephritic factor[17]. The mechanism underlying the association wasunknown. Proteinuria and end-stage renal failure hadbeen reported in type 2 FPLD before [18], but with-out renal biopsy, they were assumed to be secondaryto diabetic nephropathy.

Fig. 5 Renal biopsy revealing glomerular lesions under LM and EM. a Glomerular enlargement with average glomerular diameter being 230 μm.(LM, H&E stain, × 40). b Mild mesangial hypercellularity, without significant matrix expansion. (LM, PASM, stain, × 400). c Focal sclerosis of 1glomerulus, and exudative lesions were concomitant. (LM, PASM stain, × 400). d Segmental thickening of glomerular basement membrane andmild effacement of the podocyte foot processes, mild mesangial matrix expansion. (EM, × 8000)

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Although the majority of FSGS cases are idiopathic, anumber of genetic and familial forms of FSGS have beenrecognized, with mutations in genes encoding proteinsintegral to basement membrane and/or glomerularpodocyte function. Thong KM et al. reported a largepedigree of type 2 FPLD (with mutation in the LMNAgene), in which four members were found to havebiopsy-proven FSGS [19]. No immune complexes wereobserved, and there were no features suggesting diabeticnephropathy on biopsy. The maximum glomerular di-ameters of four patients were 142 μm, 200 μm, 206 μmand 218 μm. The LMNA gene codes for lamins A/C,major components of the nuclear lamina which functionin nuclear architecture, integrity and the regulation ofgene expression [20]. Since there was no evidence ofsecondary causes of FSGS, the association between FSGSand type 2 FPLD suggested the physiological role ofLMNA could be relevant to the maintenance of glom-erular structure and function [19].Until now, no case of renal involvement has been re-

ported in type 4 FPLD. This is the first case of protein-uria and renal biopsy in a patient with type 4 FPLD. Inthis case, the average glomerular diameter was 230 μm,suggestive of glomerulomegaly. According to a study bySamuel T et al., in histologically normal kidneys of 24males (20–69 years), the mean (SD) glomerular diameterwas 201 (28) mm (range 110–276 mm) [21]. Glomerulo-megaly could be the result of glomerular hyperfiltration,which was caused by the abnormal metabolic status inthe patient [22]. Our patient’s estimated glomerular fil-tration rate was 154 mL/min/1.73 m2. Adaptive FSGSmay be associated with excessive nephron workload inhyperfiltration status. With glomerular hypertrophy,pressure and flow in the glomeruli are increased, leadingto podocyte stress (a mismatch between glomerular loadand glomerular capacity). Podocytes compensate byhypertrophy to cover more of the glomerular capillarysurface. Increased mechanical distension and shear forceon podocytes can be a critical factor driving podocyteinjury [23]. In the EM results of this patient’s renalbiopsy tissue, mild foot process fusion and focal GBMthickness were evidence of the above hypotheticalpathogenesis. In addition, the serum albumin level of thepatient is normal, which is common in adaptive FSGSwhile unusual in primary FSGS. Adaptive FSGS usuallyresponds well to RAAS (renin–angiotensin–aldosteronesystem) antagonism, often with > 50% proteinuriareduction [24]. RAAS antagonism directly addresses thehaemodynamic alterations in adaptive FSGS. Combiningthis patient’s clinical features, pathological findings andresponse to ACEI, we deduced that the pathogenesis ofthis patient’s renal lesion was similar to obesity-associated FSGS, which was a maladaptive response tothe renal haemodynamic changes [25]. However, given

the patient’s history of insulin-resistant diabetes, theearly stages of diabetic nephropathy (Class I, Renal Path-ology Society classification, [26]) should be carefullywatched for.Regarding the patient, after 1 month of treatment with

benazepril, her renal protein excretion was decreased to0.81 g/24 h. Serum creatinine level was 40 μmol/L. Esti-mated glomerular filtration rate was 139 mL/min/1.73 m2 (Revised Schwartz Formula). Apart from RAASantagonism, management of metabolic abnormalities isalso very important. Diet and exercise form an integralpart of the treatment plan. Metformin and long-chain n-3 polyunsaturated fatty acids help alleviate insulin resist-ance and dyslipidaemia.There are some limitations of our approach to this

case. First, we only performed gene sequencing of thepatient and her parents, not the entire family, becauseher brother was abroad and other relatives were also re-mote. The mutation detected in the patient and hermother was novel. We only predicted the function of themutated gene based on existing knowledge. The co-segregation analysis of the pathogenesis of this mutationwas limited. Second, the follow-up period was only 1month. We will continue to follow the case in thefuture.

ConclusionFPLD is a group of rare disorders. To date, no case oftype 4 FPLD has been reported to have kidney disease.We reported here the first case of a type 4 FPLD patientpresenting with proteinuria. The renal biopsy revealedfeatures of glomerulomegaly and adaptive FSGS second-ary to glomerular hyperfiltration. Treatment with anACEI helped decrease renal protein excretion. For youngpatients who present with early-onset proteinuria, FPLDshould be considered in the differential diagnosis.

AbbreviationsABHD5: αβ-hydrolase domain containing 5; ACEI: Angiotensin-convertingenzyme inhibitor; ATGL: Adipose tissue triglyceride lipase; BMI: Body MassIndex; EM: Electron microscopy; FPLD: Familial partial lipodystrophy;FSGS: Focal segmental glomerulosclerosis; H&E: Haematoxylin and eosinstain; HSL: Hormone-sensitive lipase; IF: Immunofluorescence; LM: Lightmicroscopy; MCGN: Mesangiocapillary glomerulonephritis; PASM: PeriodicSchiff-methenamine stain; RAAS: Renin–angiotensin–aldosterone system

AcknowledgementsThe authors would like to acknowledge Dr. Ling Yuan for providingmagnetic resonance image interpretation for the article.

FundingThis work was supported by grants from the Chinese Academy of MedicalScience (CAMS) Initiative for Innovative Medicine (2017-I2M-2-001, 2016-I2M-1-008).

Availability of data and materialsEssential data and materials were presented in this manuscript. More clinical,laboratory, and pathological data are available from the correspondingauthor on reasonable request.

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Authors’ contributionsKZ designed the study. RXC drafted the manuscript, KZ revised themanuscript. RXC, LZ and KZ were treating physicians for the patient. WY andYBW performed pathological analysis and interpretation. NS performed genesequencing analysis and interpretation. HL, MXL and XML contributedsuggestions for the diagnosis and management of this patient. All authorsread and approved the final manuscript.

Ethics approval and consent to participateWe obtained ethics approval from the Peking Union Medical CollegeHospital review boards. The patient and her parents were informed aboutthe case report. After the discussion, the patient and her parents signedconsent forms if they wanted to participate in the study.

Consent for publicationWritten informed consent was obtained from the patient and her parents forpublication of this case report and the images in it. A copy of the writtenconsent is available. The manuscript is also approved by all authors forpublication.

Competing interestsThe authors declare that they have no competing interests.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Author details1Department of Internal Medicine, Peking Union Medical College Hospital,Chinese Academy of Medical Sciences, Beijing, China. 2Department ofNephrology, Peking Union Medical College Hospital, Chinese Academy ofMedical Sciences, Beijing, China. 3McKusick-Zhang Center for GeneticMedicine, State Key Laboratory of Medical Molecular Biology, Institute ofBasic Medical Sciences, Chinese Academy of Medical Sciences and School ofBasic Medicine Peking Union Medical College, Beijing, China. 4Presentaddress: Peking Union Medical College Hospital (East), No. 1 Shuaifuyuan,Dongcheng District, Beijing 100730, China.

Received: 3 July 2017 Accepted: 2 May 2018

References1. Hussain I, Garg A. Lipodystrophy syndromes. Endocrinol Metab Clin N Am.

2016;45(4):783–97.2. Brown RJ, Araujo-Vilar D, Cheung PT, Dunger D, Garg A, Jack M, Mungai L,

Oral EA, Patni N, Rother KI, et al. The diagnosis and Management ofLipodystrophy Syndromes: a multi-society practice guideline. J ClinEndocrinol Metab. 2016;101(12):4500–11.

3. Jeru I, Vatier C, Araujo-Vilar D, Vigouroux C, Lascols O. Clinical utility genecard for: familial partial lipodystrophy. Eur J Hum Genet. 2017;25(2). https://www.nature.com/articles/ejhg2016102/. https://doi.org/10.1038/ejhg.2016.102.

4. Kozusko K, Tsang VH, Bottomley W, Cho YH, Gandotra S, Mimmack M, LimK, Isaac I, Patel S, Saudek V, et al. Clinical and molecular characterization of anovel PLIN1 frameshift mutation identified in patients with familial partiallipodystrophy. Diabetes. 2015;64(1):299–310.

5. Gandotra S, Le Dour C, Bottomley W, Cervera P, Giral P, Reznik Y, CharpentierG, Auclair M, Delepine M, Barroso I, et al. Perilipin deficiency and autosomaldominant partial lipodystrophy. N Engl J Med. 2011;364(8):740–8.

6. Gupta N, Asi N, Farah W, Almasri J, Moreno Barrionuevo P, Alsawas M, WangZ, Haymond MW, Brown RJ, Murad MH. Clinical features and managementof non-HIV related lipodystrophy in children: a systematic review. J ClinEndocrinol Metab. 2017;102(2):363-74.

7. Brasaemle DL, Subramanian V, Garcia A, Marcinkiewicz A, Rothenberg A.Perilipin a and the control of triacylglycerol metabolism. Mol Cell Biochem.2009;326(1–2):15–21.

8. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. SeminLiver Dis. 2001;21(1):3–16.

9. Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, LassA, Madeo F. FAT SIGNALS–lipases and lipolysis in lipid metabolism andsignaling. Cell Metab. 2012;15(3):279–91.

10. Tansey JT, Sztalryd C, Gruia-Gray J, Roush DL, Zee JV, Gavrilova O, ReitmanML, Deng CX, Li C, Kimmel AR, et al. Perilipin ablation results in a leanmouse with aberrant adipocyte lipolysis, enhanced leptin production, andresistance to diet-induced obesity. Proc Natl Acad Sci U S A. 2001;98(11):6494–9.

11. Gandotra S, Lim K, Girousse A, Saudek V, O'Rahilly S, Savage DB. Humanframe shift mutations affecting the carboxyl terminus of perilipin increaselipolysis by failing to sequester the adipose triglyceride lipase (ATGL)coactivator AB-hydrolase-containing 5 (ABHD5). J Biol Chem. 2011;286(40):34998–5006.

12. Savage DB, Petersen KF, Shulman GI. Disordered lipid metabolism and thepathogenesis of insulin resistance. Physiol Rev. 2007;87(2):507–20.

13. Subramanian V, Rothenberg A, Gomez C, Cohen AW, Garcia A,Bhattacharyya S, Shapiro L, Dolios G, Wang R, Lisanti MP, et al. Perilipin amediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1adipocytes. J Biol Chem. 2004;279(40):42062–71.

14. Javor ED, Moran SA, Young JR, Cochran EK, DePaoli AM, Oral EA, TurmanMA, Blackett PR, Savage DB, O'Rahilly S, et al. Proteinuric nephropathy inacquired and congenital generalized lipodystrophy: baseline characteristicsand course during recombinant leptin therapy. J Clin Endocrinol Metab.2004;89(7):3199–207.

15. Misra A, Peethambaram A, Garg A. Clinical features and metabolic andautoimmune derangements in acquired partial lipodystrophy: report of 35cases and review of the literature. Medicine (Baltimore). 2004;83(1):18–34.

16. Mathieson PW, Wurzner R, Oliveria DB, Lachmann PJ, Peters DK.Complement-mediated adipocyte lysis by nephritic factor sera. J Exp Med.1993;177(6):1827–31.

17. Owen KR, Donohoe M, Ellard S, Clarke TJ, Nicholls AJ, Hattersley AT,Bingham C. Mesangiocapillary glomerulonephritis type 2 associated withfamilial partial lipodystrophy (Dunnigan-Kobberling syndrome). NephronClin Pract. 2004;96(2):c35–8.

18. Kobberling J, Dunnigan MG. Familial partial lipodystrophy: two types of anX linked dominant syndrome, lethal in the hemizygous state. J Med Genet.1986;23(2):120–7.

19. Thong KM, Xu Y, Cook J, Takou A, Wagner B, Kawar B, Ong AC.Cosegregation of focal segmental glomerulosclerosis in a family withfamilial partial lipodystrophy due to a mutation in LMNA. Nephron ClinPract. 2013;124(1–2):31–7.

20. Lin F, Worman HJ. Structural organization of the human gene encodingnuclear Lamin a and nuclear Lamin C. J Biol Chem. 1993;268(22):16321–6.

21. Samuel T, Hoy WE, Douglas-Denton R, Hughson MD, Bertram JF.Applicability of the glomerular size distribution coefficient in assessinghuman glomerular volume: the Weibel and Gomez method revisited.J Anat. 2007;210(5):578–82.

22. Helal I, Fick-Brosnahan GM, Reed-Gitomer B, Schrier RW. Glomerularhyperfiltration: definitions, mechanisms and clinical implications. Nat RevNephrol. 2012;8(5):293–300.

23. Kriz W, Lemley KV. A potential role for mechanical forces in the detachmentof podocytes and the progression of CKD. J Am Soc Nephrol. 2015;26(2):258–69.

24. Rosenberg AZ, Kopp JB. Focal Segmental Glomerulosclerosis. Clin J Am SocNephrol. 2017;12(3):502–17.

25. Darouich S, Goucha R, Jaafoura MH, Zekri S, Ben Maiz H, Kheder A.Clinicopathological characteristics of obesity-associated focal segmentalglomerulosclerosis. Ultrastruct Pathol. 2011;35(4):176–82.

26. Tervaert TW, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB,Ferrario F, Fogo AB, Haas M, de Heer E, et al. Pathologic classification ofdiabetic nephropathy. J Am Soc Nephrol. 2010;21(4):556–63.

Chen et al. BMC Nephrology (2018) 19:111 Page 7 of 7